What is the initial dose of norepinephrine (levarterenol) to start in a patient with septic shock?

From the Guidelines

For septic shock, start norepinephrine at 0.01-0.5 μg/kg/min as a continuous IV infusion, titrating every 5-15 minutes to maintain a mean arterial pressure (MAP) of at least 65 mmHg, as recommended by the most recent guidelines 1. The maximum dose is typically 2-3 mcg/kg/min, though higher doses may occasionally be needed. Norepinephrine should be administered through a central venous catheter whenever possible to avoid extravasation risks. Frequent blood pressure monitoring is essential during initiation and dose adjustments. Norepinephrine is the first-line vasopressor for septic shock because it increases vascular tone through alpha-1 adrenergic effects while maintaining cardiac output through its beta-1 effects, as supported by multiple studies 1. This helps restore tissue perfusion while avoiding the excessive tachycardia and potential arrhythmias associated with pure beta agonists. Some key points to consider when using norepinephrine in septic shock include:

• The optimal timing of vasopressors relative to fluid infusion has been debated, but norepinephrine is generally recommended as the first-line vasopressor agent 1
• Dopamine may be used as an alternative vasopressor agent to norepinephrine, but only in patients with low risk of tachyarrhythmias and absolute or relative bradycardia 1
• Dobutamine may be used to increase cardiac output, stroke index, and oxygen delivery, but its use is more problematic due to the risk of tachycardia and arrhythmia 1 Once the patient is stabilized, gradual weaning should occur as the underlying sepsis resolves and other supportive measures take effect. It is also important to note that the use of norepinephrine in septic shock should be guided by an individualized approach, taking into account the patient's underlying condition, response to treatment, and potential risks and benefits 1.

From the Research

Norepinephrine Dosage in Septic Shock

• The optimal dosage of norepinephrine to start in septic shock is not explicitly stated in the provided studies, but the studies suggest that early administration of norepinephrine is beneficial for septic shock patients to restore organ perfusion 2.
• A study published in 2019 found that early use of norepinephrine in septic shock resuscitation increased shock control by 6 hours compared with standard care, with a median time from emergency room arrival to norepinephrine administration of 93 minutes in the early norepinephrine group 3.
• Another study published in 2019 suggested that the combination of central venous pressure (CVP) and mean arterial pressure (MAP) can help doctors make the next decision to increase or decrease norepinephrine dosage after the initial resuscitation of septic shock 4.

Factors Influencing Norepinephrine Dosage

• The decision to increase or decrease norepinephrine dosage should be based on individual patient factors, such as CVP and MAP, as well as the patient's response to the initial dosage 4.
• The study published in 2019 also found that patients with a CVP <10 mmHg and a dMAP >0 mmHg may benefit from a decrease in norepinephrine dosage, while patients with a CVP ≥10 mmHg and a dMAP ≤0 mmHg may require an increase in norepinephrine dosage 4.

Clinical Considerations

• The use of norepinephrine in septic shock should be guided by the principles of early goal-directed therapy, which aims to optimize oxygen delivery and tissue perfusion 5.
• Clinicians should be aware of the potential risks and benefits of norepinephrine therapy, including the risk of cardiogenic pulmonary edema and new-onset arrhythmia, and should monitor patients closely for these complications 3.